1. Field of the Invention
The present invention relates to a system and method for diagnosis of sensor performance. More particularly, the present invention relates to a system and method for diagnosing sensor performance using analyte-independent ratiometric signals.
2. Description of the Related Art
Glucose sensors are an essential element in diabetes management. In particular, continuous glucose sensors provide numerous advantages over episodic glucose sensors or conventional finger-stick glucose test strips. Critical to the success of a continuous glucose sensor, however, is a determination or diagnosis of the performance of the sensor. Existing continuous glucose sensors become less sensitive over time, and eventually fail and need to be replaced. As such, it is important to monitor the performance of a continuous glucose sensor, and to replace the sensor when the performance drops below an acceptable level.
One difficulty with fluorescence measuring systems is due to the inherently noisy nature of intensity signals. Ratiometric sensing takes advantage of a very stable property of dye emission spectra. That is, the ratio of different bands within the spectra is relatively insensitive to changes in the overall intensity of the spectra. Fluctuations in emission power or optical efficiency of the system, within limits, do not affect the measured ratio between different frequency bands, provided that the chosen bands are reasonably noise-free. Continuous glucose sensors based on a fluorescently-labeled glucose binding protein (GBP) can take advantage of ratiometric sensing to obtain more accurate readings.
As shown, for example, in FIG. 1, the frequency response for a labeled GBP-based continuous glucose sensor includes an isosbestic point 100. That is, there is a frequency for which intensity response is independent of the concentration of the target analyte. The isosbestic point has been used to measure sensor performance independent of analyte concentration. The isosbestic point signal, however, has no utility in the measurement of the analyte concentration, since by its nature it does not change in response to analyte concentration. In existing ratiometric systems, different frequency bands must be measured to determine glucose concentration since the intensity at the isosbestic point does not correlate to glucose concentration. When neither of the measured frequency bands is narrowly centered on the isosbestic point of the spectra, diagnosing intensity disturbances is more difficult because both measured intensity bands change in response to both analyte concentration changes and system changes. It would be beneficial to be able to extract a noise free signal which corresponds to analyte concentration only and an analyte independent signal which corresponds to system status only, without requiring measurement of the isosbestic point in addition to at least two other frequencies. Such a combination has not been previously demonstrated with a continuous GBP detection system.
Accordingly, there is a need for a system and method for diagnosing sensor performance using analyte independent ratiometric signals. In such a system, preferably the same signals may be used for both analyte measurement and analyte-independent diagnosis, thereby minimizing system complexity and the number of measurements that must be taken. A signal pair is preferably selected to optimize the best possible analytical signal, such as for the highest signal to noise ratio over the expected analytical range, while still providing a sensor diagnostic capability.